tbuckley/cabot-search huggingface dataset:
Manganese Porphyrin‐Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from a Hydrogen Sulfide Donor
Authors: Kemper Young, Setsuko Yamane, Elmira Abbasi GharehTapeh, Shingo Kasamatsu, Hideshi Ihara, Urara Hasegawa
Journal: Advanced Healthcare Materials (2023)

Abstract Per/polysulfide species that are generated from endogenously produced hydrogen sulfide have critical regulatory roles in a wide range of cellular processes. However, the lack of delivery systems that enable controlled and sustained release of these unstable species in biological systems hinders the advancement of sulfide biology research, as well as the translation of knowledge to therapeutic applications. Here, a novel approach is developed to generate per/polysulfide species in cells by combining an H 2 S donor and manganese porphyrin‐containing polymeric micelles (MnPMCs) that catalyze oxidization of H 2 S to per/polysulfide species. MnPMCs serve as a catalyst for H 2 S oxidation in aerobic phosphate buffer. HPLC‐MS/MS analysis reveals that H 2 S oxidation by MnPMCs in the presence of glutathione results in the formation of glutathione‐SnH ( n = 2 and 3). Furthermore, co‐treatment of human umbilical vein endothelial cells with the H 2 S donor anethole dithiolethione and MnPMCs increases intracellular per/polysulfide levels and induces a proangiogenic response. Co‐delivery of MnPMCs and an H 2 S donor is a promising approach for controlled delivery of polysulfides for therapeutic applications.
Genome editing–induced t(4;11) chromosomal translocations model B cell precursor acute lymphoblastic leukemias with KMT2A-AFF1 fusion
Authors: Feng Pan, Jolanda Sarno, Johan Jeong, Xin Yang, Astraea Jager, Tanja A. Gruber, Kara L. Davis, Michael L. Cleary
Journal: Journal of Clinical Investigation (2023)

A t(4;11) leukemia model established from CRISPR-engineered chromosomal translocations between the KMT2A and AFF1 genes recapitulate proteomic, epigenomic, and transcriptomic features of primary patient leukemias.
Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice
Authors: Matt J. Matrongolo, Phillip S. Ang, Junbing Wu, Aditya Jain, Joshua K. Thackray, Akash Reddy, Chi Chang Sung, Gaëtan Barbet, Young-Kwon Hong, Max A. Tischfield
Journal: Journal of Clinical Investigation (2023)

Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associates with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup in Twist1+/-:5xFAD transgenic Alzheimer's disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion.
Outbreak of Corynebacterium diphtheriae among asylum seekers in Belgium in 2022: operational challenges and lessons learnt
Authors: Stéphanie Jacquinet, Helena Martini, Jean-Paul Mangion, Sarah Neusy, Aurélie Detollenaere, Naïma Hammami, Lien Bruggeman, Bart Hoorelbeke, Denis Pierard, Laura Cornelissen
Journal: Eurosurveillance (2023)

Since 2022, European countries have been facing an outbreak of mainly cutaneous diphtheria caused by toxigenic Corynebacterium diphtheriae among asylum seekers. In Belgium, between 1 March and 31 December 2022, 25 cases of toxigenic C. diphtheriae infection were confirmed among asylum seekers, mostly among young males from Afghanistan. Multi-locus sequence typing showed that most isolates belonged to sequence types 574 or 377, similar to the majority of cases in other European countries. The investigation and management of the outbreak, with many asylum seekers without shelter, required adjustments to case finding, contact tracing and treatment procedures. A test-and-treat centre was organised by non-governmental organisations, the duration of the antimicrobial treatment was shortened to increase compliance, and isolation and contact tracing of cases was not possible. A vaccination centre was opened, and mobile vaccination campaigns were organised to vaccinate a maximum of asylum seekers. No more cases were detected between end December 2022 and May 2023. Unfortunately, though, three cases of respiratory diphtheria, including one death, were reported at the end of June 2023. To prevent future outbreaks, specific attention and sufficient resources should be allocated to this vulnerable population, in Belgium and at international level.
PCR testing of traced contacts for SARS-CoV-2 in England, January to July 2021
Authors: Toby Nonnenmacher, Niharika Dandamudi, Matthias Erwin Futschik, Sarah A Tunkel, Raghavendran Kulasegaran-Shylini, Nick Germanacos, Joanna Cole-Hamilton, Edward Blandford, Ashley Goddard, Joe Hillier, Stephen Finer, Susan Hopkins, Tom Fowler
Journal: Eurosurveillance (2023)

Background The NHS Test and Trace (NHSTT) programme was established in May 2020 in England to deliver SARS-CoV-2 testing and contact tracing in order to identify infected individuals and reduce COVID-19 spread. To further control transmission, people identified as contacts were asked to self-isolate for 10 days and test only if they became symptomatic. From March 2021, eligibility criteria for PCR testing expanded to include asymptomatic contacts of confirmed cases. Aim To analyse testing patterns of contacts before and after the change in testing guidance in England to assess the impact on PCR testing behaviour with respect to symptom status and contact type. Methods Testing and contact tracing data were extracted from the national data systems and linked. Subsequently, descriptive statistical analysis was applied to identify trends in testing behaviour. Results Between 1 January and 31 July 2021, over 5 million contacts were identified and reached by contact tracers; 42.3% took a PCR test around the time they were traced. Overall positivity rate was 44.3% and consistently higher in symptomatic (60–70%) than asymptomatic (around 20%, March–June) contacts. The proportion of tests taken by asymptomatic contacts increased over time, especially after the change in testing guidance. No link was observed between uptake of PCR tests and vaccination coverage. Fully vaccinated contacts showed lower positivity (23.8%) than those with one dose (37.2%) or unvaccinated (51.0%). Conclusion Almost 1 million asymptomatic contacts were tested for SARS-CoV-2, identifying 214,056 positive cases, demonstrating the value of offering PCR testing to this group.
Outbreaks of autochthonous Dengue in Lazio region, Italy, August to September 2023: preliminary investigation
Authors: Gabriella De Carli, Fabrizio Carletti, Martina Spaziante, Cesare Ernesto Maria Gruber, Martina Rueca, Pietro Giorgio Spezia, Valentina Vantaggio, Alessandra Barca, Claudio De Liberato, Federico Romiti, Maria Teresa Scicluna, Stefania Vaglio, Mariano Feccia, Enrico Di Rosa, Francesco Paolo Gianzi, Cristina Giambi, Paola Scognamiglio, Emanuele Nicastri, Enrico Girardi, Fabrizio Maggi, Francesco Vairo
Journal: Eurosurveillance (2023)

Between August and September 2023, three distinct autochthonous dengue virus transmission events occurred in Lazio, Italy, with the main event in Rome. The events involved three different dengue serotypes. No link with previous imported cases was identified. Here we describe the epidemiological and phylogenetic analysis of the first autochthonous cases and the implemented control actions. The multiple transmission events call for a strengthening of the vector control strategies and future research to better characterise the risk in countries like Italy.
Metoclopramide Nasal Spray in Women with Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study
Authors: Richard W. McCallum, Henry P. Parkman, Ronnie Fass, Bal R. Bhandari, Marilyn R. Carlson, Raymond D. Buck
Journal: Clinical Gastroenterology and Hepatology (2023)
Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study
Authors: Sarah L Gorst, Nina Seylanova, Susanna R Dodd, Nicola L Harman, Margaret O'Hara, Caroline B Terwee, Paula R Williamson, Dale M Needham, Daniel Munblit, Timothy R Nicholson, Olalekan L. Aiyegbusi, Athena Akrami, Christian Apfelbacher, Melanie Calvert, Jessica Chen, Anastasia Chernyawskaya, Vicky Fallon, Shamil Haroon, Sarah E. Hughes, Allison Jaure, Alisa Kokorinia, Melina Michelen, Piero Olliaro, Callum Parr, Alexandra Pokrovskaya, Nile Saunders, Jochen Schmitt, Ian Shemilt, Louise Sigfrid, Frances Simpson, Manoj Sivan, Charitini Stavropoulous
Journal: The Lancet Respiratory Medicine (2023)
Structure-function analysis of tight junction-directed permeation enhancer PIP250
Authors: Alistair Taverner, Khaled Almansour, Kate Gridley, Ana Rita Lima Marques, Julia MacKay, Ian M. Eggleston, Randall J. Mrsny
Journal: Journal of Controlled Release (2023)

The intestinal paracellular route of absorption is modulated via tight junction (TJ) structures located at the apical neck of polarized intestinal epithelial cells to restrict solute movement through the intercellular space between them. Tight junctions open or close in response to changes in the phosphorylation status of light chain (MLC) at position Ser-19. This phosphorylation event is primarily controlled by MLC kinase (MLCK) and MLC phosphatase (MLCP), the latter being a holoenzyme that involves interaction between protein phosphatase 1 (PP1) and myosin targeting protein 1 (MYPT1). An entirely D-amino acid Permeant Inhibitor of Phosphatase (PIP) peptide sequence designed to disrupt PP1-MYPT1 interactions at the cytoplasmic surface of TJs, PIP250 (rrfkvktkkrk) localized at intracellular TJ structures, altered expression levels of specific TJ proteins, increased cellular phosphorylated MLC (pMLC) levels, binding to PP1, decreased epithelial barrier function, and significantly increased systemic uptake of the poorly absorbed antibiotic gentamicin in vivo. A series of PIP250 peptide analogues showed that positions phe3 and val5 were critical to its functional properties, with some providing opportunities to tune the dynamic actions of its TJ modulation properties. These data confirm the activity of PIP250 as a rationally designed oral permeation enhancer and validated key amino acids involved in its interaction with PP1 that define its overall actions; the magnitude and duration of these enhancing properties were associated with the MYPT1-mimetic properties of the PIP250 peptide analogues described.
Disease-specific corona mediated co-delivery of MTX and siRNA-TNFα by a polypeptide nanoplatform with antigen-scavenging functions in psoriasis
Authors: Xiaofei Xin, Yong Zhou, Yifu Lyu, Ying Zhu, Di Wu, Jingjing Li, Chao Qin, Lifang Yin
Journal: Journal of Controlled Release (2023)
Effects of polydimethylsiloxane membrane surface treatments on human uterine smooth muscle cell strain response
Authors: Elizabeth E. Marr, Brett C. Isenberg, Joyce Y. Wong
Journal: Bioactive Materials (2023)

In the United States, 1 in 10 infants are born preterm. The majority of neonatal deaths and nearly a third of infant deaths are linked to preterm birth. Preterm birth is initiated when the quiescent state of the uterus ends prematurely, leading to contractions and parturition beginning as early as 32 weeks, though the origins are not well understood. To enable research and discovery of therapeutics with potential to better address preterm birth, the capability to study isolated cell processes of pregnant uterine tissue in vitro is needed. Our development of an in vitro model of the myometrium utilizing human uterine smooth muscle cells (uSMCs) responsible for contractions provides a methodology to examine cellular mechanisms of late-stage pregnancy potentially involved in preterm birth. We discuss culture of uSMCs on a flexible polydimethylsiloxane (PDMS) substrate functionalized with cationic poly-l-lysine (PLL), followed by extracellular matrix (ECM) protein coating. Previous work exploring uSMC behavior on PDMS substrates have utilized collagen-I coatings, however, we demonstrated the first exploration of human uSMC response to strain on fibronectin-coated flexible membranes, importantly reflecting the significant increase of fibronectin content found in the myometrial ECM during late-stage pregnancy. Using the model we developed, we conducted proof-of-concept studies to investigate the impact of substrate strain on uSMC cell morphology and gene expression. It was found that PLL and varied ECM protein coatings (collagen I, collagen III, and fibronectin) altered cell nuclei morphology and density on PDMS substrates. Additionally, varied strain rates applied to uSMC substrates significantly impacted uSMC gene expression of IL-6, a cytokine associated with instances of preterm labor. These results suggest that both surface and mechanical properties of in vitro systems impact primary human uSMC phenotype and offer uSMC culture methodologies that can be utilized to further the understanding of cellular pathways involved in the uterus under mechanical load.
Magnetic resonance imaging in diagnostics changes in the spine and spinal cord in children with achondroplasia
Authors: K. A. Diachkov, G. V. Diachkova, A. M. Aranovich, O. G. Prudnikova
Journal: Radiology - Practice (2023)

The article presents the possibilities of MRI in assessing spinal deformities responsible for neurological symptoms, as well as for detecting pathological changes in the spinal cord in 35 patients with achondroplasia. An analysis of the MRI semiotics of pathological changes in the spine in patients with achondroplasia indicates their extreme polymorphism and varying degrees of severity. Anatomical deviations from the norm in the structure of the spine of patients with achondroplasia include more than 15 manifestations, the frequency of which is different and ranges from 17 to 100 % in the examined patients. Changes associated with etiological causes predominate, dystrophic changes are much less common in patients aged 15-18 years.
Non-invasive left ventricular pressure-volume loops from cardiovascular magnetic resonance imaging and brachial blood pressure: validation using pressure catheter measurements
Authors: Per M Arvidsson, Peregrine G Green, William D Watson, Mayooran Shanmuganathan, Einar Heiberg, Giovanni Luigi De Maria, Håkan Arheden, Neil Herring, Oliver J Rider
Journal:  (2023)

Abstract Aims Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. A non-invasive method for the computation of PV loops from magnetic resonance imaging and brachial cuff blood pressure has recently been proposed. Here we evaluated the fidelity of the non-invasive PV algorithm against invasive LV pressures in humans. Methods and results Four heart failure patients with EF &amp;lt; 35% and LV dyssynchrony underwent cardiovascular magnetic resonance (CMR) imaging and subsequent LV catheterization with sequential administration of two different intravenous metabolic substrate infusions (insulin/dextrose and lipid emulsion), producing eight datasets at different haemodynamic states. Pressure-volume loops were computed from CMR volumes combined with (i) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, or (ii) invasive pressures averaged from 19 to 30 sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Non-invasively derived PV loop parameters demonstrated high correlation and low bias when compared to invasive data for stroke work (R2 = 0.96, P &amp;lt; 0.0001, bias 4.6%), potential energy (R2 = 0.83, P = 0.001, bias 1.5%), end-systolic pressure-volume relationship (R2 = 0.89, P = 0.0004, bias 5.8%), ventricular efficiency (R2 = 0.98, P &amp;lt; 0.0001, bias 0.8%), arterial elastance (R2 = 0.88, P = 0.0006, bias −8.0%), mean external power (R2 = 0.92, P = 0.0002, bias 4.4%), and energy per ejected volume (R2 = 0.89, P = 0.0001, bias 3.7%). Variations in estimated end-diastolic pressure did not significantly affect results (P &amp;gt; 0.05 for all). Intraobserver analysis after one year demonstrated 0.9–3.4% bias for LV volumetry and 0.2–5.4% for PV loop-derived parameters. Conclusion Pressure-volume loops can be precisely and accurately computed from CMR imaging and brachial cuff blood pressure in humans.
A Self‐Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration
Authors: Zhangzhe Zhou, Yang Liu, Wenjing Li, Zhijian Zhao, Xiaowei Xia, Junlin Liu, Yaoge Deng, Yubin Wu, Xiangqiang Pan, Fan He, Huilin Yang, Weihong Lu, Yong Xu, Xuesong Zhu
Journal: Advanced Healthcare Materials (2023)

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.
The inhibition of inner mitochondrial fusion in hepatocytes reduces non-alcoholic fatty liver and improves metabolic profile during obesity by modulating bile acid conjugation
Authors: Lorenzo Da Dalt, Annalisa Moregola, Monika Svecla, Silvia Pedretti, Francesca Fantini, Mirko Ronzio, Patrizia Uboldi, Diletta Dolfini, Elena Donetti, Andrea Baragetti, Nico Mitro, Luca Scorrano, Giuseppe Danilo Norata
Journal: Cardiovascular Research (2023)

Abstract Aims Mitochondria are plastic organelles that continuously undergo biogenesis, fusion, fission, and mitophagy to control cellular energy metabolism, calcium homeostasis, hormones, sterols, and bile acids (BAs) synthesis. Here, we evaluated how the impairment of mitochondrial fusion in hepatocytes affects diet-induced liver steatosis and obesity. Methods and results Male mice selectively lacking the key protein involved in inner mitochondrial fusion, optic atrophy 1 (OPA1) (OPA1ΔHep) were fed a high fat diet (HFD) for 20 weeks. OPA1ΔHep mice were protected from the development of hepatic steatosis and obesity because of reduced lipid absorption; a profile which was accompanied by increased respiratory exchange ratio in vivo, suggesting a preference for carbohydrates in OPA1ΔHep compared to controls. At the molecular level, this phenotype emerged as a consequence of poor mitochondria-peroxisome- endoplasmic reticulum (ER) tethering in OPA1 deficient hepatocytes, which impaired BAs conjugation and release in the bile, thus impacting lipid absorption from the diet. Concordantly, the liver of subjects with non-alcoholic fatty liver disease (NAFLD) presented an increased expression of OPA1 and of the network of proteins involved in mitochondrial function when compared with controls. Conclusion Patients with NAFLD present increased expression of proteins involved in mitochondrial fusion in the liver. The selective deficency of OPA1 in hepatocytes protects mice from HFD-induced metabolic dysfunction by reducing BAs secretion and dietary lipids absorption as a consequence of reduced liver mitochondria-peroxisome-ER tethering.
C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis
Authors: Peter N Taylor, Kimberly S Collins, Anna Lam, Stephen R Karpen, Brianna Greeno, Frank Walker, Alejandro Lozano, Elnaz Atabakhsh, Simi T Ahmed, Marjana Marinac, Esther Latres, Peter A Senior, Mark Rigby, Peter A Gottlieb, Colin M Dayan, Carla Greenbaum, Jeffrey Krisher, Jay Skyler, Diane Wherrett, Ulf Hannelius, Anton Lindqvist, Christoph Nowak, Ionut Bebu, Barbara Braffett, Antonella Napolitano, Salim Jan Mohamed, Gordon Weir, Gerald Nepom, Roy Beck, Claudia Richard, Joseph Hedrick, Johnny Ludvigsson, Matthias Von Herrath, Francisco Leon, Eleanor Ramos, Parth Narendran, Stephen Gitelman, Dana Dabelea, Rob Andrews, Michael Haller, Elizabeth Jensen, Kevan Harold, Jan Dutz
Journal: The Lancet Diabetes & Endocrinology (2023)

Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes.
Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial
Authors: Quincy Chu, Francesco Perrone, Laurent Greillier, Wei Tu, Maria Carmela Piccirillo, Federica Grosso, Giuseppe Lo Russo, Marie Florescu, Manlio Mencoboni, Alessandro Morabito, Fabiana Letizia Cecere, Giovanni Luca Ceresoli, David E Dawe, Paolo Andrea Zucali, Maria Pagano, John R Goffin, Myriam Locatelli Sanchez, Cesare Gridelli, Gerard Zalcman, Xavier Quantin, Virginie Westeel, Piera Gargiulo, Sara Delfanti, Dongsheng Tu, Christopher W Lee, Natasha Leighl, Joana Sederias, Pamela Brown-Walker, Yiwen Luo, Sylvie Lantuejoul, Ming-Sound Tsao, Arnaud Scherpereel, Penelope Bradbury, Scott A Laurie, Lesley Seymour
Journal: The Lancet (2023)